Support is requested for a Keystone Symposia meeting entitled Mitochondria, Metabolism and Heart Failure, organized by Richard N. Kitsis, Gerald W. Dorn II and Rong Tian. The meeting will be held in Santa Fe, New Mexico from January 27-February 1, 2015. The most common causes of heart failure are coronary artery disease, high blood pressure, and diabetes. Mitochondrial perturbations have been associated with heart failure itself, and with most of the other preceding risk factors. In some cases, mitochondrial dysfunction may play a causal role while in others mitochondria are a central target responsible for organ dysfunction. Understanding mitochondrial pathophysiology and identifying ways to ameliorate mitochondrial dysfunction is critical to therapy for cardiovascular disease. Therefore, the overall objectives of this meeting are (i) to mechanistically connect the fundamental biology of metabolism and mitochondrial function with the pathogenesis of heart failure, a major cause of morbidity and mortality in the world; and (ii) to increase basic understanding of metabolism and mitochondrial function using observations in cardiac muscle, a traditional platform for these studies. The ongoing convergence of the cardiac metabolism and mitochondrial biology fields provides a particularly cogent rationale for this meeting; moreover, large gaps of knowledge exist in this area such as the precise molecular signaling that connects metabolism and energy sensing with mitochondrial function, and the roles of basic mitochondrial processes (e.g. biogenesis, fission, fusion, mitophagy, maintenance of mitochondrial genome integrity) in metabolism and heart failure. These deficiencies in fundamentally important scientific knowledge and their clinical implications for a common and lethal disease confer exceptional significance on this conference, which is relevant to the NHLBI mission with respect to the role of mitochondria in metabolic function. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Diabetes and Metabolic Dysfunction, which will share a Keynote Address and three plenary sessions.